Corneal stroma-derived mesenchymal stem cells(CS-MSCs) are mainly distributed in the anterior part of the corneal stroma near the corneal limbal stem cells(LSCs). CS-MSCs are stem cells with self-renewal and multidire...Corneal stroma-derived mesenchymal stem cells(CS-MSCs) are mainly distributed in the anterior part of the corneal stroma near the corneal limbal stem cells(LSCs). CS-MSCs are stem cells with self-renewal and multidirectional differentiation potential. A large amount of data confirmed that CS-MSCs can be induced to differentiate into functional keratocytes in vitro, which is the motive force for maintaining corneal transparency and producing a normal corneal stroma. CS-MSCs are also an important component of the limbal microenvironment. Furthermore, they are of great significance in the reconstruction of ocular surface tissue and tissue engineering for active biocornea construction. In this paper, the localization and biological characteristics of CS-MSCs, the use of CS-MSCs to reconstruct a tissue-engineered active biocornea, and the repair of the limbal and matrix microenvironment by CS-MSCs are reviewed, and their application prospects are discussed.展开更多
Non-small cell lung cancer(NSCLC)remains a major cause of cancer-related mortality worldwide,emphasizing the need for novel therapeutic strategies.In this study,we demonstrate that homoyessotoxin(hYTXs),a marine-deriv...Non-small cell lung cancer(NSCLC)remains a major cause of cancer-related mortality worldwide,emphasizing the need for novel therapeutic strategies.In this study,we demonstrate that homoyessotoxin(hYTXs),a marine-derived natural compound,exerts potent anti-NSCLC progression.Network pharmacology,molecular docking,molecular dynamics simulations,and SPR analysis confirmed a strong binding affinity between hYTXs and EGFR.Mechanistically,hYTXs disrupted EGFR trafficking by accelerating its endocytosis and enhancing its accumulation within lysosomes,thereby accelerating receptor degradation without altering EGFR mRNA levels.CHX chase and lysosomal inhibition assays further verified that hYTXs downregulated EGFR through post-translational regulation.This degradation led to suppression of downstream PI3K/AKT/ERK signaling,reduced phosphorylation of FOXO3a and p70S6K,and enhanced PTEN nuclear translocation.Functionally,hYTXs induced apoptosis,oxidative stress,S-phase arrest,mitochondrial dysfunction,and DNA damage in A549 cells,with comparable inhibitory potency in EGFR-mutant lines(PC9,H1975)but minimal cytotoxicity toward normal lung epithelial cells.In vivo,hYTXs significantly inhibited tumor growth and exhibited excellent safety based on serum biochemistry and lung histology.Collectively,hYTXs represents a promising next-generation EGFR-targeting compound that overcomes kinase-mutation-driven resistance by promoting receptor degradation rather than kinase inhibition.展开更多
基金Supported by the National Key R&D Program of China (No.2016YFC1100100)the Key R&D Program of Shaanxi Province (No.2018ZDXM-SF-056)+2 种基金the Health and Family Planning Research Fund Project of Shaanxi Province (No.2016C004)the Key Research and Development Program of Shaanxi Province (No.2019SF-196)the Research Talent Project of Xi’an Municipal Health Commission (No.J201902037)。
文摘Corneal stroma-derived mesenchymal stem cells(CS-MSCs) are mainly distributed in the anterior part of the corneal stroma near the corneal limbal stem cells(LSCs). CS-MSCs are stem cells with self-renewal and multidirectional differentiation potential. A large amount of data confirmed that CS-MSCs can be induced to differentiate into functional keratocytes in vitro, which is the motive force for maintaining corneal transparency and producing a normal corneal stroma. CS-MSCs are also an important component of the limbal microenvironment. Furthermore, they are of great significance in the reconstruction of ocular surface tissue and tissue engineering for active biocornea construction. In this paper, the localization and biological characteristics of CS-MSCs, the use of CS-MSCs to reconstruct a tissue-engineered active biocornea, and the repair of the limbal and matrix microenvironment by CS-MSCs are reviewed, and their application prospects are discussed.
基金supported by the Shenzhen Science and Technology Program(KCXFZ20230731093402005)the National Key R&D Program of China(2023YFA0914300(2023YFA0914302))the program of the Shenzhen Key Laboratory of Advanced Technology for Marine Ecology(ZDSYS20230626091459009).
文摘Non-small cell lung cancer(NSCLC)remains a major cause of cancer-related mortality worldwide,emphasizing the need for novel therapeutic strategies.In this study,we demonstrate that homoyessotoxin(hYTXs),a marine-derived natural compound,exerts potent anti-NSCLC progression.Network pharmacology,molecular docking,molecular dynamics simulations,and SPR analysis confirmed a strong binding affinity between hYTXs and EGFR.Mechanistically,hYTXs disrupted EGFR trafficking by accelerating its endocytosis and enhancing its accumulation within lysosomes,thereby accelerating receptor degradation without altering EGFR mRNA levels.CHX chase and lysosomal inhibition assays further verified that hYTXs downregulated EGFR through post-translational regulation.This degradation led to suppression of downstream PI3K/AKT/ERK signaling,reduced phosphorylation of FOXO3a and p70S6K,and enhanced PTEN nuclear translocation.Functionally,hYTXs induced apoptosis,oxidative stress,S-phase arrest,mitochondrial dysfunction,and DNA damage in A549 cells,with comparable inhibitory potency in EGFR-mutant lines(PC9,H1975)but minimal cytotoxicity toward normal lung epithelial cells.In vivo,hYTXs significantly inhibited tumor growth and exhibited excellent safety based on serum biochemistry and lung histology.Collectively,hYTXs represents a promising next-generation EGFR-targeting compound that overcomes kinase-mutation-driven resistance by promoting receptor degradation rather than kinase inhibition.
